Peptides are short chains of amino acids that make up the building block of proteins. They are essential signaling molecules in the body that play a crucial role in regulating vital biological processes like hormone production, tissue repair, and metabolism. Many have been proven to improve collagen synthesis, enhance skin proliferation, decrease inflammation, and even decrease appetite.1 Bioactive peptides are specific, highly targeted peptide sequences that exert beneficial effects on human health.2 Their biological effects often include lowering blood pressure, reducing inflammation, and regulating hormones. These peptides first came into the marketplace in 1920, in the form of insulin. Peptides have rapidly grown, most recently with Glucagon-like peptide-1 (GLP-1s) to slow digestion, regulate blood sugar, and increase the feelings of fullness for diabetes and weight management. The U.S. Food and Drug Administration (FDA) has currently approved over 100 peptides and peptide-based drugs, with over 34 new peptide drugs from 2016-2024, and a large uptick in 2025 of 46 new peptide drugs.3 However, thousands of unapproved synthetic peptides exist in what is referred to as the “gray market” of supplements. Current FDA-Approved Peptides in the Marketplace Peptides have demonstrated significant clinical potential across a range of therapeutic applications, with several peptide-based therapies now established in the treatment of metabolic, skeletal, and other chronic diseases. Examples include: GLP-1 receptor agonists that have extensive large-scale phase III human trials proving efficacy in reducing food noise, managing blood sugar, and achieving a significant level of weight loss. Teriparatide, a synthetic peptide of the parathyroid hormone is used for bone building to treat severe osteoporosis and is prescribed to post-menopausal women. Tesamorelin has been proven to reduce excess abdominal fat in HIV patients with lipodystrophy. As demand grows, so do emerging markets for target-specific peptides, such as anti-aging.  However, the FDA has not approved any peptides for anti-aging and longevity. Potential Risks and Side Effects of Peptides Like all drugs, GLP-1s come with risks and side effects. Common side effects of GLP-1s include nausea, vomiting, and diarrhea. More rare side effects include low blood sugar, lung aspiration, thyroid cancer, and gallstones. In addition to weight loss, GLP-1s can also cause muscle loss. Some of these side effects may turn into long-term problems that can continue for months or even years after discontinuing use of a GLP-1, such as pancreatitis, vision problems, acute kidney injury, blurry vision and acute gallbladder disease. These side effects can vary based on the type of GLP-1 that is taken, as well as the duration.   Certain peptide therapies like GLP-1s can deplete the body of important minerals like calcium, iron, magnesium, potassium, and zinc. Many people are unaware that there are nutritional interventions that can be added to support the body during peptide therapies. This level of detailed safety information, side effects, and supporting nutritional interventions on GLP-1s only exists because they have been available since 2005, while also being extensively and continuously studied. However, for all unregulated peptides, these same safety risks, side effects, and long-term health impacts remain  unknown. Grey Market Peptides Peptides existing within the “grey market” are not FDA-approved. Rather, they are typically marketed as “research purposes only,” “not for human consumption,” or “research peptides” and lack any federal regulations on their manufacturing and distribution. These peptides carry risks of contamination, lack of clinical evidence for efficacy, and unverified evidence on dosing. Some of the more popular peptides highly demanded in the grey market include BPC-157, marketed for use in tissue repair, gut health, and wound healing. For example, Thymosin Beta-4 is in high demand by athletes and body builders to aid in muscle recovery, reducing inflammation, and for tissue regeneration. MOTS-C is a mitochondrial-derived peptide highly regarded in the biohacking community for cellular metabolism and energy. One of the biggest issues with unregulated peptides is the fact that little scientific evidence exists backing these claims. The practice of large-scale clinical trials for safety and efficacy for grey market peptides does not exist. Without clinical trials, any evidence of acute and long-term side effects  go unreported. The efficacy of peptides can vary dramatically based on the compound and its intended use. Additionally, non-FDA approved peptides carry risk of contamination from heavy metals such as arsenic or lead.4  While most pharmacies will adhere to FDA guidelines, there is a grey zone between navigating the ever-changing regulatory landscape and what they can compound. Therefore, compounding pharmacies have become a source of purchasing peptides, but most unregulated peptides are purchased from online vendors selling “research use only” peptides. Online testing labs are posting results of different vendors distributing peptides to help buyers make more informed decisions. These companies look mainly at the purity of peptides, rating them from good to poor, but no lab regulations for testing these peptides exist. On one testing website, they have eliminated all liability based on what the user does with the testing information provided. There are hundreds of vendors selling peptides, many of which have been ranked as poor quality or fraudulent, meaning that the peptide they marketed the product as was not in the product at all. While the level of contamination in these peptides is unknown, there have been several cases of contaminated peptides. One such case in Australia impacted 6 people with acute liver toxicity, leading one female to acute liver failure requiring a liver transplant from a counterfeit injectable advertised as the experimental weight-loss drug Retatrutide.5 Considering Nutritional Interventions as Alternatives to Injectable Peptides Before peptide drugs existed, the only source of peptides available were consumed through foods. Foods naturally high in dietary peptides include protein-rich foods, meats, fermented dairy, whole grains, legumes and even certain seeds like hemp and flax. Flaxseed oil contains specific dietary peptides known as cyclolinopeptides or orbitides. Locating sources utilizing unique extraction methods to preserve peptides from animal organs can be an excellent source of dietary peptides. Consuming peptides is not to take away from the therapeutic relevance of pharmaceutical peptides that are very specifically targeted at high therapeutic dosages for injection. Weight Loss The most popular applications of therapeutic peptides are for weight loss, anti-aging, and cellular repair. Evidence-informed dietary and lifestyle practices can contribute to the health and resilience of these areas. These are all actionable steps one can take before reaching for an unregulated peptide. For example, certain foods can stimulate GLP-1 secretion or help maintain its activity in the body. Compounds in bitter foods that can activate certain receptors in the gut that help stimulate GLP-1s through endocrine signaling. Bitter foods with this effect are Arugula, dandelion greens, bitter melon, kale, mustard greens and herbs like gentian and berberine. Unfortunately, modern day breeding techniques have caused bred plants to be less bitter to favor more palatability for the consumer. GLP-1s may impact gastric emptying, alter gastric acidity, and negatively impact the gut microbiome. GLP-1 signaling inhibits gallbladder contraction and can impair emulsification of dietary fats, which can contribute to deficiencies in fat soluble vitamins and impact overall nutrient status. It is unknown how other peptides may impact or deplete the body of key nutrients. Refer to a previously written Wholistic Matters article on nutritional and botanical support for GLP-1 activity for more information. Fiber supplements and herbs like ginger, hops, wormwood, and feverfew can support healthy gastric juice output and increase bile flow for optimal digestion and absorption within the gut to activate GLP-1s. Anti-Aging and Longevity Herbs with adaptogenic properties that are high in antioxidants, polyphenols and flavonoids can provide great anti-aging support. Ginseng can promote collagen and hyaluronic acid production within the skin.6 Ginkgo Biloba can aid in skin health by providing antioxidant protection and reducing inflammation. Astaxanthin, a naturally occurring carotenoid pigment found in microalgae, is a powerful antioxidant studied for its benefits in skin health and anti-aging.7 Existing clinical evidence shows astaxanthin fighting off inflammation by targeting specific inflammatory biomarkers and signaling pathways.8 This makes it ideal as a recovery aid to support athletic performance. A different study demonstrates that astaxanthin can support anti-aging by inhibiting enzymes like MMP-1 that degrade collagen and elastin.7 Choosing to consume whole foods containing powerful phytochemicals can combat the signs of aging. For instance, foods such as berries and mushrooms can fight aging by lowering inflammation and providing antioxidants such as glutathione and anthocyanins to protect the cells from oxidative stress. Lutein is another powerful antioxidant found in dark green leafy vegetables that provides anti-aging benefits by protecting the skin while suppressing systemic inflammation.9 Stress Management & Sleep Hygiene Stress is a huge factor that contributes to aging, chronic disease, and inflammation. Providing adequate nutrition for the body through whole food sources and adequate protein is vital for cellular health. Herbs like Ashwagandha, skullcap, St. John's Wort (SJW), Schisandra, and Saffron can aid in promoting relaxation and reducing stress. (St. John’s Wort is known to interact with certain medications. Anyone taking prescription medications should consult their prescribing physician before beginning this herb.) Nutrients from omega fatty acids and a vitamin B complex can provide support to a body combating stress. When derived from whole food sources, minerals like magnesium, iron, and zinc can be utilized in the body easily due to their high bioavailability and ability to cross the blood brain barrier.10 Whole food sources of magnesium can be found in crops like Swiss chard and buckwheat. Healthy aging goes hand in hand with sleep quality. Aiming for 7-9 hours a night is ideal to allow the body and mind to be repaired. Vitamin D and B vitamins are essential support for a healthy circadian rhythm. Herbal support could include Valerian root and Passionflower, both having a long historical use to aid in sleep quality and relaxation. Additionally, exercise and movement have been consistently proven to support anti-aging, weight loss, and substantially reduce risk of chronic disease. Exercise recovery can be supported with adequate nutrition of whole foods and protein.  Those with a busy lifestyle could try adding a whey or plant-based protein shake. Adequate hydration with electrolytes and supporting joints with glucosamine, Manganese, and Boswellia can also aid in recovery. Boswellia Serrata resin has long standing use in its ability to support join pain and stiffness.11 But pairing Boswellia with glucosamine and Manganese provides additional benefits in the prevention of cartilage degradation and inflammation.12 Discontinuation of Peptide Usage Once the body discontinues and clears peptides from the system, the benefits tend to gradually diminish. For example, those taking GLP-1s may regain weight and see blood sugar levels start to gradually increase.13 This is why it remains crucial to build a healthy foundation of nutrition and lifestyle habits to combat the loss of benefits the peptide may have provided. Prioritize whole foods with adequate protein, fiber, and healthy fats. Commit to daily movement and prioritize sleep and hydration. Get additional support from a functional medicine doctor that can help track progress and order appropriate lab tests as needed. The discontinuation of unregulated peptides will likely diminish benefits of reduced inflammation, faster workout recovery, and more. Peptides that have been around for a substantial number of years may have long term safety studies conducted, but unregulated peptides are widely unknown for their safety profiles of long-term usage. Supplement Considerations as Alternatives to Peptides Support for Healthy Aging Gingko standardized to contain active flavonglycosides, ginkgolides and bilobalides combined with ginseng, containing ginseng root and standardized to contain active ginsenosides. Look for added ingredients of antioxidants, such as grape seed extract Astaxathin combined with organic whole foods such as beet and mountain spinach for antioxidant support.  Lutein, paired with buckwheat juice powder, holy basil leaf and tuna oil powder to support skin elasticity and appearance. Support for weight management and glucose regulation Hops flower CO2 extract standardized to containing active alpha and beta acids, with feverfew containing active parthanolide is a modern formulation of traditional herbs to support healthy GLP-1 secretion and satiety. Fiber powder containing both soluble and insoluble fiber with whole food sources of oat, beet and carrot fiber, apple pectin, sweet potato and rice bran can maintain healthy blood sugar levels that are within normal range. Support for Exercise Recovery Look for a non-denatured whey protein sourced from a company that tests protein powders for heavy metals and microbial contaminants. Boswellia serrata combined with bovine bone, glucosamine, manganese and whole foods such as reishi mushroom, shiitake mushroom, flaxseed oil, Spanish moss, inositol and pea vine juice powder to help support healthy connective tissue and joint health. Find a turmeric supplement combined with fenugreek fiber for optimal absorption and highest bioavailability of curcuminoids to combat inflammation. Support for Stress Management and Sleep Look for a magnesium product that contains whole food sources like Swiss chard and buckwheat for optimal bioavailability and absorption. Fish oils from wild caught sustainable sources Valerian root and rhizome extract, combined with passionflower herb and jujube seed to aid in promoting relaxation and mild nervous tension.   Did you know WholisticMatters is powered by Standard Process? Learn more about Standard Process’ whole food-based nutrition philosophy.   Supplements for Healthcare Practitioners Join a community of 60,000+ like-minded healthcare professionals. A relationship with Standard Process offers networking opportunities, and an array of educational resources and tools to help grow your practice.  Learn more

How phytonutrients in whole foods can calm inflammation that contributes to age-related conditions The risk for disease and co-morbidities has sky-rocketed in recent years among aging populations. This is due to numerous factors such as dysregulated innate immunity, cell senescence, prolific reactive oxygen species (ROS), accumulation of “self-debris ” or dead cell material, and microbiome dysbiosis, that both contributes to and exacerbates what we now know as inflammaging.1-3 What is Inflammaging? Inflammaging is the chronic display of low-grade inflammation, occurring without infection or pro-inflammatory stimuli, that degrades tissue and further contributes to the acceleration of age-related conditions such as Alzheimer’s, atherosclerosis, diabetes, sarcopenia, and osteoporosis.1,2  Such inflammation is becoming more common, where in theory, it should subside immediately after the pathogen or the acute inflammatory stimuli has been addressed, allowing the tissue to rest, repair, and heal. This chronic state of inflammation, however, weakens and degrades the tissue, making it less resilient and more prone to further assault and injury, which further weakens the body systems and body overall.1 This type of chronic inflammation causes hyperactivity of the innate immune system (broad-spectrum immunity) which is already upregulated as adaptive immunity (targeted immunity) decreases naturally with age.2,3 This dysregulation impairs the body’s natural ability to efficiently and effectively respond to incoming antigens or environmental stimuli and maintain homeostatsis.3 Cytokines An over-active immune system leads to the over-production of cytokines and other inflammatory mediators, where an abundance of cytokines weaken the anabolic signaling, or tissue building, cascade which may downregulate insulin, erythropoietin, and other hormone signaling which inhibits protein synthesis and may further attribute to sarcopenia or osteoarthristis.1,2,4 Furthermore, other pro-inflammatory cytokines have been attributed to age-related endocrine dysfunction, metabolic and digestion disruption, as well as cognitive decline, dementia, and other neurodegenerative conditions.3  Adipokines Adipokines, or adipose-specific derived cytokines, have also been shown to trigger the proliferation of adipose tissue, which also recruits additional pro-inflammatory cytokines to these tissues. In other words, adipose tissue increases with age and accumulates in or around the liver, bones, muscles, as well as other organ tissues, and further triggers an inflammatory cascade response. This inflammatory cascade causes more cytokines to be directed to localized tissue, further promotes more accumulation of adipose in these organs, and the cycle continues, creating a now systemic pro-inflammatory environment. Macrophages Another inflammatory mediator, macrophages- normally involved in acute inflammation, have also been shown to be more abundant and prolific in age-related inflammation. They infiltrate the adipose tissue and, like adipokines, induce adipose accumulation, trigger adipose inflammation - or the release of adipokines, and further contribute to systemic inflammation.3 Other tissues, such as the muscles, kidney, heart, liver, and brain commonly experience elevated levels of macrophages during aging, though it is thought macrophages in these areas attribute to more of a localized pro-inflammatory response. Microglias However, like cytokines, microglias, or brain-specific macrophages, trigger yet another inflammatory cascade, and have also been attributed to the onset of dementia, again, demonstrating the link between inflammaging and age-related conditions.3 Interestingly, a recent Japanese study on semi-supercenternarians, those who are between 105-109 years old, concluded that chronic systemic inflammation was a major factor in loss of cognitive function and overall mortality. The absence of inflammation was a greater predictor of longevity more so than telomere length, the length of the repetitive sequence at the end of a DNA strand, which has been previously established as the predictor of successful aging.3 Telomere length, along with cell damage and oxidative stress, are some of the potential mechanisms attributed to cell senescence. Cell senescence, or the irreversible end of the cell-cycle where the cell is no longer able to replicate, also triggers the release of various pro-inflammatory cytokines. It is thought that this pro-inflammatory response at the end of a cell’s life is the original cause of inflammaging and the corresponding age-related conditions.1 Detoxification Pathways in Aging Populations Additionally, it has been shown that the clearance of these now dead cells, slows the progression of, and may even prevent, age-related conditions, such as atherosclerosis and osteoarthritis.1 However, clearance of this dead material, or self-debris, is challenging as the number of cell deaths increase with age, as well as the pathways of clearance and elimination also decrease with age. These cellular components, such as free radicals, and metabolites, are recognized by a series of “hazard” sensors, called inflammasomes, that again trigger a pro-inflammatory response in the hopes of debris clearance and/or cellular repair. When a cell is damaged or dies, the inflammasomes cause a release of mitochondria-specific reactive oxygen species (ROS) that initiate their own highly potent inflammatory cascade loop, causing further inflammation and damage to the cell and surrounding tissues.1 The ability for the cell to handle oxidative stress and other reactive species is well-functioning in youth but declines or malfunctions as we age, also resulting in the activation of the pro-inflammatory response system.3 As the damaged cells accumulate, the “hazard” response becomes chronic, and further triggers a maladapted, highly inflammatory response that further alters the microenvironment of the surrounding tissue.1 Gut Microbiome Another microenvironment modulated by inflammaging is the gut microbiome. While it has been shown that the presence of Bifidobacterium is inversely correlated to serum levels of inflammatory cytokines, it has also been documented that these and other anti-inflammatory/health promoting microbiota decrease with age. To add to this, the more pro-inflammatory and pathogenic species have also been found to increase with age. These pro-inflammatory changes in gut microbiota may also increase the susceptibility of infection and pathological colonization of undesirable microbiota in this population.1 Furthermore, these detrimental microbiota produce other inflammatory byproducts and metabolites that leach into the surrounding tissue and eventually end up in circulation, causing- and exacerbating- damage along the away. In fact, this increased microbial translocation has been shown to result in endotoxemia, destruction of the vascular integrity, altered blood flow or stasis, and atherosclerosis. Of course, the body also loses the ability to control and sequester these microbes and their metabolites with age, further contributing to this dysbiosis.2 Oral Dysbiosis It's not just the gut microbiota that is contributing to inflammaging, the oral microbiota is also a contributing factor. Oral dysbiosis, in combination with the body’s natural degradation of the gums over time and maladjusted inflammatory response, has been shown to both cause and worsen gingivitis and periodontal disease. The presence of these conditions has been linked to a significant decline in quality of life, as well as specific age-related pathologies such as cardiovascular disease, endothelial dysfunction, metabolic dysfunction, diabetes, and neurodegenerative diseases due to the spillover of inflammatory cytokines from the periodontium into circulation. Oral dysbiosis also increases the risk of periodontal pathogens that can further impede and modulate the immune system, while creating a more favorable environment for these opportunistic microbes to thrive. Furthermore, as the periodontal tissue deteriorates over time, the inflammatory response starts to malfunction thus triggering a flood of cytokines to the localized tissue and causes yet another inflammatory cascade loop. This inflammatory cascade then triggers even more tissue degradation and cell death, exacerbating it further.5 However, there is hope. It’s not all doom and gloom as inflammaging is both preventable and curable.2 Phytonutrients in Whole Foods and Their Influence on Inflammaging Dietary choices, good or bad, are believed to have a major influence on both the development and progression of age-related diseases. In particular, the Mediterranean diet, which is high in polyphenols, has been shown to profoundly modulate the systemic inflammatory response by inhibiting the production of such inflammatory metabolites and further protect against other pro-inflammatory damage. A diet such as this could potentially attenuate age-related diseases, improve cell metabolism and systemic outcomes, and further promote overall quality of life.6 In fact, adherence to this diet has been largely associated with decrease pain, disability, and depression as well as an increase in physical performance, cognitive function, and overall vitality.4 Whole Food Nutrition: The Mediterranean Diet The Mediterranean diet is a well-balanced diet, characterized by consistent use of olive oil, vegetables, fruits, nuts, legumes, whole grains, and seafood as well as the moderate inclusion of eggs, dairy, and other lean proteins. It also emphasizes the importance of restricting saturated fats, red meats, processed foods, refined grains, and sugar. All in all, it provides a well-balanced mix of antioxidants and anti-inflammatory components, as well as comprehensive microbiome support such as prebiotic compounds and beneficial fiber.6,7 Polyphenols: Resveratrol, Catechins, and Flavonoids As mentioned earlier, this diet is high in polyphenols and other phytonutrients which have developed in an evolutionary way to protect the plant from pathogens, insects, animals, etc. A similar cell-defense mechanism is imparted to us humans upon consumption of these phytonutrients.6 Some of these phytonutrients and polyphenols include resveratrol- found in grapes, catechins- found in green tea, and flavonoids, such as quercetin - found in dark berries, dark chocolate, and citrus fruits. These compounds have been extensively studied and their numerous mechanisms of action can be distilled down to the potent and direct antioxidant activity that occurs at the intra-cellular level, as well as the inhibition of cytokine activity, the regulation and modulation of gene expression, and the activation of additional anti-inflammatory cascades. Essentially, they have far-reaching benefits and have been notably recognized for their promotion and protection of the cardiovascular system, nervous system, musculoskeletal system, immune system, and beyond.8 Clinical Takeaways In conclusion, while the compounding factors of inflammaging such as a dysregulated immune system, self-debris proliferation, and microbiome dysbiosis are incredibly detrimental, a change in diet could potentially alleviate, prevent, and reverse this type of chronic inflammation. The Mediterranean diet, based on adequate intake of olive oil, vegetables, fruits, legumes, and seafood, is high in polyphenols and microbiome-promoting compounds, and may ease the overall process of aging and inflammation. The compounds associated with the Mediterranean diet support cell integrity and metabolism, free-radical scavenging, and proper immune response, which further promotes healing, self-regulation, and repair of damaged tissue and organ structures. Adherence to this diet may then attenuate disease and, more importantly, improve longevity and quality of life.   Did you know WholisticMatters is powered by Standard Process? Learn more about Standard Process’ whole food-based nutrition philosophy.   Learn More About Standard Process

In this lively conversation, Dr. Besuden, DC, CFMP, shares all of her tips, tricks and recommendations for aging optimally and gracefully. Drs. Sarah and Besuden discuss strategies for maintaining healthy habits and routines for practitioner and patient alike. This episode is full of gems including specific supplementation to fill nutrition gaps, easy-to-maintain exercise routines, and a deep dive into hormesis practices.